An important step in determining the biological compatibility and safety of a medical device as required by ISO 10993 is chemical characterization. Extractables and leachables testing is a vital but complex part of this. There is no one-size-fits-all approach that can be universally applied to all products, and the success of an extractables and leachables study relies heavily on the experience and skill of those conducting it. This blog post explores the most common mistakes in extractables and leachables testing.
1. Incorrect Sample Selection
As with any analytical process, proper sample selection in extractables and leachables testing is essential for accurate results. In order to establish the safety of a given product, quantitative analysis of leachable compounds must be carried out to determine their concentrations. For this to be accurate, the prepared sample must be a proportional representation of the product itself: this means that the sample must contain the same proportions of each material as the product itself. If the medical device contains 5% nylon, then the sample must be also. Ideally this means that the optimum way to perform the analysis is to analyze the medical device itself in its final finished format.
2. Poor Solvent Choice
Following sample preparation comes the extraction phase, whereby compounds are extracted from the sample using solvents of varying polarity. At this point there are a few important factors to bear in mind. Current best practice is to perform an exhaustive extraction or exaggeration of the use conditions of the product depending on the products use conditions. This is often done using a three solvent study consisting of polar, mid-polar and non-polar solvents.
Depending on the results from the extrables study, a “simulated-use” extraction may also be required; where the simulated use study is designed to emulate the use conditions of the product.
In all studies, the solvent must be compatible with the analytical methods being used to identify the extracted compounds. Solvent exchanges may be required prior to instrumental analysis, in which appropriate controls should be in place to justify a valid exchange, with no compound loss.
Finally, it’s also vital that the extraction conditions – including the solvent – don’t produce any changes to the sample chemistry that wouldn’t occur under the use conditions.
3. Neglecting Analysis Blanks and Control Samples
It can be easy to overlook the fact that the solvents and reaction vessels used in extractables and leachables testing will typically contain contaminants. The presence of these contaminants must be accounted for during the interpretation of results to provide accurate results.
Analysis blanks are controls containing only the pure extraction solvent without exposure to the sample. It’s crucial that the analysis blank is placed into the same type of extraction vessel and exposed to exactly the same conditions and processing steps as the samples.
Negative controls such as instrument blanks or known reference materials can be used to confirm the cleanliness of the analytical system. These controls help to establish that analysis systems are free of extractable components, or conversely, to demonstrate that a detected component didn’t arise from the sample.
4. Failing to Identify Unknown Compounds
While this is undoubtedly one of the most common mistakes, it’s also a challenging area of study. No single analytical technique exists which can be used to identify all extractable compounds. The proper selection and use of different techniques and the thorough interpretation and analysis of results remains a highly skilled task.
RQM+ Lab Services draws on over four decades of analytical chemistry expertise to offer a world-class extractables and leachables testing service. Our team of expert chemists can carry out accurate and detailed extractables and leachables testing for any application using state-of-the-art instrumentation.